Mixed results in Alzheimer’s trials but continued enthusiasm for the amyloid hypothesis and the development of treatments

Mixed results in Alzheimer’s trials but continued enthusiasm for the amyloid hypothesis and the development of treatments

24Jul

2015

Mixed results in Alzheimer’s trials but continued enthusiasm for the amyloid hypothesis and the development of treatments

At the Alzheimer’s Association International Conference (AAIC) this week in Washington DC, Biogen and Eli Lilly presented results from their latest Alzheimer’s disease clinical trials.

Biogen caused a great deal of excitement earlier this year when they released data from a Phase 1b clinical trial using an antibody to remove amyloid from the brain (see President’s blog of March 2015). Study results using doses of 1, 3 and 10mg indicated that early intervention in the disease might lead to modification of the disease by attenuating cognitive decline. At the AAIC meeting Biogen presented additional results from a 6mg dose. While their studies show that high doses of 10mg can positively affect test of cognition, several adverse events were reported at this dose. Biogen still has confidence in their approach and will go on to take the next important step – a future Phase 3 trial, in which they will enroll more patients and determine whether it is possible to identify a therapeutic dose that leads to limited adverse events.

Eli Lilly reported on follow-on studies from two previous clinical trials, also using an antibody intended to remove amyloid. Their results showed that patients that had previously been on a placebo but then switched to active drug never caught up with patients who were dosed on active drug at an earlier time point. Lilly executives suggest that this finding provides clear evidence that their drug acts in a disease-modifying manner. We will await the outcomes of future studies – Expedition 3 from Lilly, and the Biogen Phase 3 trial – to see whether these drugs do indeed lead to disease modification.

Regardless of the outcome of these studies they provide considerable additional support for the amyloid hypothesis of Alzheimer’s disease and the possibility of developing disease-modifying drugs based on amyloid clearance. The amyloid hypothesis is based on strong human genetic evidence but had been challenged by earlier clinical trial failures. There are now diverse studies being performed on an array of targets in Alzheimer’s disease, including the GliaCure ongoing Phase 1b trial in patients. It is surely now just a matter of time until we find treatments that are both successful and safe for the patient population.